NM_130848.3:c.175C>T

Variant names:

• chr5-135446934-G-A
• rs749183149
• NM_130848.3:c.175C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_130848.3(DCANP1):​c.175C>T​(p.Pro59Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P59A) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: DCANP1 NM_130848.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.392

Genes affected

DCANP1 (HGNC:24459): (dendritic cell associated nuclear protein 1) This intronless gene is specifically expressed in dendritic cells (DCs), which are potent antigen-presenting cells involved in activating naive T cells to initiate antigen-specific immune response. The encoded protein is localized mainly in the perinucleus. One of the alleles (A/T) of this gene, that causes premature translation termination at aa 117, has been associated with an increased prevalence of major depression in humans. [provided by RefSeq, Jul 2008]

TIFAB (HGNC:34024): (TIFA inhibitor) Involved in several processes, including animal organ morphogenesis; cranial nerve development; and hard palate morphogenesis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08596662).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCANP1	NM_130848.3	c.175C>T	p.Pro59Ser	missense_variant	Exon 1 of 1	ENST00000503143.3	NP_570900.1
TIFAB	NM_001099221.2	c.*2520C>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000537858.2	NP_001092691.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCANP1	ENST00000503143.3	c.175C>T	p.Pro59Ser	missense_variant	Exon 1 of 1	6	NM_130848.3	ENSP00000421871.1
TIFAB	ENST00000537858	c.*2520C>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_001099221.2	ENSP00000440509.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152238 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152238 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74384

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.1
DANN	Benign	0.77
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0079	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PROVEAN	Pathogenic	-8.0	D
REVEL	Benign	0.054
Polyphen		0.50	P
Vest4		0.081
MutPred		0.088		Loss of loop (P = 0.0112);
MVP		0.16
MPC		0.055
ClinPred		0.13	T
GERP RS		-0.46
Varity_R		0.43
gMVP		0.055

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs749183149; hg19: chr5-134782624;